Current Technological Development of Antibody Therapeutics

Monoclonal antibodies are now major therapeutic agents used to treat many cancers, immunological and other diseases. Two big technological breakthroughs have enabled us to utilize monoclonal antibodies as therapeutic agents; the establishment of monoclonal antibody production technology using hybridomas, and the reduction of immunogenicity by using chimeric, humanized, and fully-human antibodies. These technological improvements have led to the successful launch of more than 25 therapeutic antibodies, such as rituximab, trastuzumab, cetuximab, adalimumab and ustekinumab, which are on the market and contribute to the health of many patients. Despite the clinical success of these antibodies, we have also been faced with demands for improvement of the antibody's therapeutic efficacy as a result of insufficient clinical efficacy seen in many clinical trials. The major mechanisms underlying the therapeutic effects of antibodies are thought to be neutralization of antigen function and/or Fc-mediated functions e.g. antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among various efforts being made to enhance the intrinsic capacity of therapeutic antibodies, the most promising is Fc engineering, including amino acid mutation, or modification of the Fc-linked oligosaccharide structures to dramatically improve Fc-mediated functions, ADCC, CDC and the FcRnmediated antibody half-life. Some Fc engineered therapeutic antibodies are evaluated in the clinic. This review will focus on the current progress made in the development of Fc engineered antibodies.